CN106220559B - N-3- pyridine acyl-dehydroabietylamine derivatives and its preparation method and application - Google Patents
N-3- pyridine acyl-dehydroabietylamine derivatives and its preparation method and application Download PDFInfo
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- CN106220559B CN106220559B CN201610597221.0A CN201610597221A CN106220559B CN 106220559 B CN106220559 B CN 106220559B CN 201610597221 A CN201610597221 A CN 201610597221A CN 106220559 B CN106220559 B CN 106220559B
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- dehydroabietylamine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 claims abstract description 33
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 60
- 238000006243 chemical reaction Methods 0.000 abstract description 22
- 210000004027 cell Anatomy 0.000 abstract description 15
- 239000000706 filtrate Substances 0.000 abstract description 10
- 238000003756 stirring Methods 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- 239000000047 product Substances 0.000 abstract description 7
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 abstract description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 abstract description 6
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 abstract description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 abstract description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 abstract description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 abstract description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 4
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- 231100000614 poison Toxicity 0.000 abstract description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 239000000243 solution Substances 0.000 description 9
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
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- 238000011160 research Methods 0.000 description 6
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 6
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 244000248349 Citrus limon Species 0.000 description 3
- 235000005979 Citrus limon Nutrition 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 150000004753 Schiff bases Chemical class 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
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- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- QUUCYKKMFLJLFS-UHFFFAOYSA-N Dehydroabietan Natural products CC1(C)CCCC2(C)C3=CC=C(C(C)C)C=C3CCC21 QUUCYKKMFLJLFS-UHFFFAOYSA-N 0.000 description 1
- NFWKVWVWBFBAOV-UHFFFAOYSA-N Dehydroabietic acid Natural products OC(=O)C1(C)CCCC2(C)C3=CC=C(C(C)C)C=C3CCC21 NFWKVWVWBFBAOV-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000222727 Leishmania donovani Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 241000222481 Schizophyllum commune Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- WREBNDYJJMUWAO-LWYYNNOASA-N [(1r,4ar,4br,10ar)-1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)[C@@H](CCC(C(C)C)=C3)C3=CC[C@H]21 WREBNDYJJMUWAO-LWYYNNOASA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
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- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007265 chloromethylation reaction Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- NFWKVWVWBFBAOV-MISYRCLQSA-N dehydroabietic acid Chemical compound OC(=O)[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 NFWKVWVWBFBAOV-MISYRCLQSA-N 0.000 description 1
- 229940118781 dehydroabietic acid Drugs 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
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- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses N-3- pyridine acyl-dehydroabietylamine derivatives and its preparation method and application.The preparation method comprises the following steps: 1) take HOBT, acidum nicotinicum or 6- methyl acidum nicotinicum are dissolved with ethyl acetate, 0 DEG C of stirring 0.5h；DCC, 0 DEG C of reaction 2.5h is added；2) it takes dehydroabietylamine to be dissolved in ethyl acetate, is then added dropwise to step 1) reaction system, react at room temperature 8h；Ice bath stirring half an hour, so that DCU is sufficiently precipitated；3) it is filtered to remove DCU, filtrate is diluted, uses 5%NaHCO3, 10% citric acid wash respectively 2-3 times, finally use saturated common salt water washing；The ethyl acetate layer dry 2h of anhydrous sodium sulfate；3) it filters, filtrate is evaporated off ethyl acetate, obtains yellow solid product.N-3- pyridine acyl-dehydroabietylamine derivatives of the invention, preparation method is simple, and product purity is high; yield is high, and biological activity test confirms, has good poisonous activity to tumour cell; there is very low toxicity to normal cell simultaneously, will have a wide range of applications in the preparation of antitumor drugs.
Description
Technical field
The invention belongs to organic compound technical fields, and in particular to N-3- pyridine acyl-dehydroabietylamine derivatives and its
Preparation method and application.
Background technique
Dehydroabietylamine also known as dehydroabietylamine are a kind of main modified products of rosin, while being also the master of disproportionated rosin amine
Want ingredient.The property of dehydroabietylamine is highly stable, optical activity is larger, this is all the physical chemistry that other rosin derivatives do not have
Property.Nowadays dehydroabietylamine is already used to prepare fungicide and mould inhibitor etc. in force, be primarily due to it have it is excellent
Bioactivity.In addition to this, dehydroabietylamine analog derivative by as metal inhibitor, lube oil additive, preservative etc. also very
Generally.It suffers from every field and is widely applied, and has covered the various aspects of our daily lifes.
Dehydroabietylamine N-C derivative quantity accounts for the ratio highest of dehydroabietylamine modified compound total amount.Dehydroabietylamine with it is interior
Ester type compound reaction produces de- under dehydroabietylamine propionic acid, dehydroabietylamine and monoxone can be obtained under conditions of pH is greater than 7
Hydrogen abietyl amine acetic acid, these are all N-C derivatives.The phase interaction of dehydroabietylamine acetic acid and metal ion is studied by infra-red sepectrometry
With the discovery anionic metals such as dehydroabietylamine acetic acid and vanadium, chromium and molybdenum can form jelly in aqueous solution.Dehydroabietylamine has
Machine part has good lipophilicity, may serve as surfactant after connecting hydrophilic radical.From disproportionated rosin amine, divide
From dehydroabietylamine sterling is obtained, it is novel to have obtained two kinds as intermediate for dimethyl dehydroabietylamine, and have simultaneously yin,
The betaines surfactant of positive two kinds of ionic natures.Dehydroabietylamine amide derivatives are to Leishmania donovani and kirschner
Trypanosome has good inhibitory activity.
Dehydroabietylamine isocyanide is a kind of derivative of the dehydroabietylamine containing N=C=O in structure, its synthetic method is more
Sample, one is using the dehydroabietic acid in rosin as parent, by obtained from O=C-Cl, reaction of sodium azide；One is in chlorine
To change under palladium and CO, dehydroabietylamine can directly synthesize dehydroabietylamine isocyanide, but the condition needs of this reaction are controlled, because
The yield of this reaction is influenced by various aspects, such as reaction temperature, reactant concentration, reaction dissolvent influence.In addition to above two
Outside method, dehydroabietylamine and phosgene reaction also available above-mentioned product.Dehydroabietylamine can be condensed with the substance containing carbonyl and give birth to
At schiff bases, schiff bases contains this structure fragment of C=N, and there are many report for studying such compound, generally to dehydroabietylamine
Amino modified is all from this thinking.It is why more to its research, be because itself have it is stronger antitumor
Cell activity and using it as ligand synthesis metal complex life activity it is also particularly excellent.It is thin to lung adenocarcinoma cell, the National People's Congress
Born of the same parents' lung carcinoma cell and human colon cancer cell have very strong inhibiting effect.Dehydroabietylamine schiff base compounds have metal good
Sustained release performance.
Due to being connected with isopropyl and a hexatomic ring on dehydroabietylamine phenyl ring, overall space is larger, and benzene modification is relatively difficult,
So research in this respect compare it is less.Dehydrogenated rosin nitrile is raw material, through chloromethylation and inorganic cyanide displacement reduction
After reaction, dehydroabietylamine derivatives can be generated, nylon can use these derivatives to modify, and can accomplish effectively to sterilize
And anti-corrosion.Dehydroabietylamine aromatic ring is modified, it is found that it is easy to that sulfonating reaction occurs, and only occur on specific position,
Thus obtained sulfonated derivative has good antiulcer activity.Nitro class aromatic derivatives have schizophyllum commune, gauffer mould
Certain inhibitory effect has excellent inhibition to some strains, such as these microorganisms of Escherichia coli, staphylococcus aureus
Activity shows biocidal property.What we studied is N-C derivative, currently without the anti-liver cancer and anti-to such compound, ovarian cancer resistance
With the active research of Human umbilical vein endothelial cells.
Summary of the invention
Goal of the invention: the deficiencies in the prior art are directed to, the object of the present invention is to provide a kind of N-3- pyridine acyls-
Dehydroabietylamine derivatives meet the use demand of anti-tumor drug.It is a further object of the present invention to provide above-mentioned N-3- pyridine acyls
Base-dehydroabietylamine derivatives preparation method.Further object of the present invention is to provide above-mentioned N-3- pyridine acyl-dehydroabietylamine and spreads out
The application of biology.
Technical solution: in order to realize foregoing invention, the technical solution adopted by the present invention are as follows:
N-3- pyridine acyl-dehydroabietylamine derivatives, structural formula are as follows:
In formula, R1For H, CH3, Cl.
A kind of N-3- pyridine acyl-dehydroabietylamine derivatives method described in synthesis, steps are as follows:
1) HOBT, acidum nicotinicum or 6- methyl acidum nicotinicum, 6- chloro-3-pyridyl formic acid are taken, is dissolved with ethyl acetate,
0 DEG C of stirring 0.5h；DCC, 0 DEG C of reaction 2.5h is added；
2) it takes dehydroabietylamine to be dissolved in ethyl acetate, is then added dropwise to step 1) reaction system, react at room temperature 8h；Ice bath
Half an hour is stirred, so that DCU is sufficiently precipitated；
3) it is filtered to remove DCU, filtrate is diluted, uses 5%NaHCO3, 10% citric acid wash respectively 2-3 times, finally with saturation
Brine It；The ethyl acetate layer dry 2h of anhydrous sodium sulfate；
4) it filters, filtrate is evaporated off ethyl acetate, obtains yellow solid product.
N-3- pyridine acyl-dehydroabietylamine derivatives the application in preparation of anti-tumor drugs.
Beneficial effect, compared with prior art, N-3- pyridine acyl-dehydroabietylamine derivatives of the invention, preparation method
Simply, product purity is high, and yield is high, and biological activity test confirms, has good poisonous activity to tumour cell, while to just
Normal cell has very low toxicity, will have a wide range of applications in the preparation of antitumor drugs.
Detailed description of the invention
Fig. 1 is the infrared spectrogram of dehydroabietylamine (a), acidum nicotinicum (b) and compound 1 (c)；
Fig. 2 is dehydroabietylamine (a), 6- methyl-acidum nicotinicum (b) and compound 2 (c) infrared spectrogram；
Fig. 3 is the infrared spectrogram of dehydroabietylamine (a), 6- chloro-3-pyridyl formic acid (b) and compound 3 (c).
Specific embodiment
The present invention is described further combined with specific embodiments below.
Embodiment 1
N-3- pyridine acyl-dehydroabietylamine (compound 1) preparation method:
1) 1.23g acidum nicotinicum is added in 100mL flask, 1.35g HOBT is dissolved, 0 DEG C with 40mL ethyl acetate
Stir 0.5h.2.06g DCC, 0 DEG C of reaction 2.5h is added.2.85g dehydroabietylamine is dissolved in 10mL ethyl acetate, by this solution
It is added dropwise to reaction system, reacts at room temperature 8h.Finally, ice bath stirring half an hour, so that DCU is sufficiently precipitated.
2) it is filtered to remove DCU, filtrate is diluted to 200mL, uses 20mL 5%NaHCO respectively3, 10% lemon pickling of 20mL
It washs 2-3 times, finally uses 20mL saturated common salt water washing.The ethyl acetate layer dry 2h of anhydrous sodium sulfate.
3) it filters, filtrate is evaporated off ethyl acetate, obtains pale yellow powder 3.05g, yield 78.2%.
Product is characterized, the infrared spectrum of dehydroabietylamine, acidum nicotinicum and compound 1, as shown in Figure 1, dehydrogenation
The absorption peak 3400cm of abietyl amine amino-1With the absorption peak 1707cm of acidum nicotinicum carboxyl-1It disappears, illustrates after the reaction
Generate novel substance；3426cm-1For the N-H stretching vibration characteristic absorption peak of amide；2927cm-1It is the opposition of methyl and methylene
Claim stretching vibration peak；1647cm-1For the C=O characteristic absorption peak of amide；1542cm-1For the N-H characteristic absorption peak of amide.
The specific data of the structural characterization of compound 1 are as follows:1H NMR(CDCl3, 600MHz) and δ (ppm): 1.03 (3H, s, H-
, 1.22~1.24 19) (9H, m, H-16,17,20), 1.36~1.81 (7H, m, H-1 α, 2,3,6), 1.99~2.01 (1H, m,
H-5), 2.30 (1H, brd, J=13.2Hz, H-1 β), 2.79~2.93 (3H, m, H-7,15), 3.34~3.49 (2H, m, H-
18), 6.50 (1H, t, J=6Hz, 22-CONH), 6.88 (1H, s, H-14), 6.98 (1H, d, J=12Hz, H-12), 7.16
(1H, d, J=7.8Hz, H-11), 7.46~9.12 (4H, m, H-25,26,24,23)；13C NMR(CDCl3, 151MHz) and δ
(ppm): 18.61,18.80,19.13,23.94,23.96,25.38,30.36,33.42,36.48,37.56,37.74,
38.35,45.83,50.42,123.58,123.95,124.19,126.96,130.59,134.61,135.19,145.72,
146.94,147.59,152.10,165.69；IR (KBr): 3426 (N-H), 2927 (- CH3,-CH2), 1647 (0=C-N),
1542(N-H)；MS (ESI) m/z:391.58 [1+H]+, 413.42 [1+Na]+。
Embodiment 2
N-6- methyl -3- pyridine acyl-dehydroabietylamine (compound 2) synthetic method:
1) 0.342g 6- methyl acidum nicotinicum, 0.337g HOBT, with 20mL ethyl acetate are added in 100mL flask
Dissolution, 0 DEG C of stirring 0.5h.0.515g DCC, 0 DEG C of reaction 2.5h is added.0.71g dehydroabietylamine is dissolved in 10mL ethyl acetate
In, this solution is added dropwise to reaction system, reacts at room temperature 8h.Finally, ice bath stirring half an hour, so that DCU is sufficiently precipitated.
2) it is filtered to remove DCU, filtrate is diluted to 200mL, uses 20mL 5%NaHCO respectively3, 10% lemon pickling of 20mL
It washs 2-3 times, finally uses 20mL saturated common salt water washing.The ethyl acetate layer dry 2h of anhydrous sodium sulfate.
3) it filters, filtrate is evaporated off ethyl acetate, obtains yellow powder 0.7326g, yield 72.53%.
Product is characterized, dehydroabietylamine, 6- methyl-acidum nicotinicum and 2 infrared spectrum as shown in Fig. 2, dehydrogenation
The absorption peak 3400cm of abietyl amine amino-1With 6- methyl-acidum nicotinicum carboxyl absorption peak 1704cm-1It disappears after the reaction,
Illustrate to have generated novel substance；3419cm-1For the N-H stretching vibration characteristic absorption peak of amide；2927cm-1It is methyl and methylene
Antisymmetric stretching vibration peak；1645cm-1For the C=O characteristic absorption peak of amide；1540cm-1For the N-H characteristic absorption of amide
Peak.
The specific data of the structural characterization of compound 2 are as follows:1H NMR(CDCl3, 600MHz) and δ (ppm): 0.987 (3H, s, H-
, 1.20~1.25 19) (9H, m, H-16,17,20), 1.33~1.78 (7H, m, H-1 α, 2,3,6), 1.93~1.97 (1H, m,
H-5), 2.28 (1H, brd, J=12.6Hz, H-1 β), 2.56~2.62 (3H, m, H-27), 2.77~2.93 (3H, m, H-7,
15), 3.29~3.44 (2H, m, H-18), 6.46 (1H, t, J=6Hz, 22-CONH), 6.86 (1H, s, H-14), 6.98 (1H,
D, J=9.6Hz, H-12), 7.14~7.18 (2H, m, H-11,25), 7.96 (1H, d, J=10.2Hz, H-26), 8.827 (1H,
S, H-23)；13C NMR(CDCl3, 151MHz) and δ (ppm): 18.63,18.81,19.13,24.01,24.40,25.45,30.41,
33.44,36.43,37.54,37.82,38.33,45.74,50.34,123.23,123.93,124.23,126.97,127.81,
134.68,135.62,145.66,146.98,147.14,161.48,165.92；IR (KBr): 3419 (N-H), 2927 (-
CH3,-CH2), 1645 (0=C-N), 1540 (N-H)；MS (ESI) m/z:405.42 [2+H]+, 427.33 [2+Na]+。
Embodiment 3
N-6- chloro-3-pyridyl acyl group-dehydroabietylamine (compound 3) synthetic method:
1) 0.393g 6- chlorine acidum nicotinicum is added in 100mL flask, 0.337g HOBT is molten with 20mL ethyl acetate
Solution, 0 DEG C of stirring 0.5h.0.515g DCC, 0 DEG C of reaction 2.5h is added.0.71g dehydroabietylamine is dissolved in 10mL ethyl acetate,
This solution is added dropwise in reaction system, 8h is reacted at room temperature.Finally, ice bath stirring half an hour, so that DCU is sufficiently precipitated.
2) it is filtered to remove DCU, filtrate is diluted to 200mL, uses 20mL 5%NaHCO respectively3, 10% lemon pickling of 20mL
It washs 2-3 times, finally uses 20mL saturated common salt water washing.The ethyl acetate layer dry 2h of anhydrous sodium sulfate.
3) it filters, filtrate is evaporated off ethyl acetate, obtains white powder 0.7687g, yield 72.52%.
Product is characterized, the infrared spectrum of dehydroabietylamine, 6- chloro-3-pyridyl formic acid and compound 3 as shown in figure 3,
The absorption peak 3400cm of dehydroabietylamine amino-1With the absorption peak 1683cm of 6- chloro-3-pyridyl formic acid carboxyl-1Disappear after the reaction
It loses, illustrates to have generated novel substance；3440cm-1For the N-H stretching vibration characteristic absorption peak of amide；2927cm-1It is methyl and methylene
The antisymmetric stretching vibration peak of base；1658cm-1For the C=O characteristic absorption peak of amide；1586cm-1It is inhaled for the N-H feature of amide
Receive peak.
The specific data of the structural characterization of compound 3 are as follows:1H NMR(CDCl3, 600MHz) and δ (ppm): 1.01 (3H, s, H-
, 1.21~1.23 19) (9H, m, H-16,17,20), 1.31~1.81 (7H, m, H-1 α, 2,3,6), 1.93~2.04 (1H, m,
H-5), 2.30 (1H, brd, J=12.6Hz, H-1 β), 2.77~2.95 (3H, m, H-7,15), 3.30~3.46 (2H, m, H-
18), 6.33 (1H, t, J=6Hz, 22-CONH), 6.88 (1H, s, H-14), 6.99 (1H, d, J=9.6Hz, H-12), 7.16
(1H, d, J=7.8Hz, H-11), 7.37 (1H, s, H-25), 8.02 (1H, d, J=10.2Hz, H-26), 8.714 (1H, s, H-
23)；13C NMR(CDCl3, 151MHz) and δ (ppm): 18.59,18.80,19.13,23.99,25.42,25.55,30.36,
32.64,33.44,33.83,36.47,37.54,37.61,37.80,38.30,45.77,50.52,123.99,124.21,
124.41,126.98,129.44,134.59,137.91,145.75,146.91,147.86,154.13,164.83；IR
(KBr): 3440 (N-H), 2927 (- CH3,-CH2), 1658 (0=C-N), 1586 (N-H)；MS (ESI) m/z:425.25 [3+H]+,
447.33[3+Na]+。
4 biological activity test of embodiment
1) using the inhibiting effect of mtt assay research 1,2 and 3 couple of Hela of compound.
Concrete operations: the Hela cell to be tested of logarithmic growth phase is configured to 105The single cell suspension of a/milliliter,
It is inoculated on 96 well culture plates, 100 microlitres of every hole, in volume fraction in 5% carbon dioxide, saturated humidity, 37 DEG C of incubators
Culture one day；Later, the sample to be tested of 100 microlitres of various concentrations is added on culture plate, every kind of concentration is 2 multiple holes；
After continuing culture for 24 hours, every hole adds 20 microlitres of MTT dyeing liquor, continues to cultivate 4h in the incubator, carefully removes supernatant liquor,
Then every hole adds 200 microlitres of THF, after half an hour fullys shake, measures OD sample value at 595nm wavelength in microplate reader, experiment
Blank group is to replace sample with the DMEM culture solution of 100 microlitres of serum-frees, and absorbance value at this moment is OD blank value, passes through public affairs
Formula (1) calculates sample to HepG2 cell inhibitory rate:
M=1-n=1-ODSample/ODBlank (1)
In formula, m: inhibiting rate；N: cell survival rate.
Then by formula (2), IC is calculated50:
lgIC50=a-b (c- (3-d-e)/4) (2)
In formula, a:lg maximum concentration；B:lg (maximum concentration/adjacent concentration)；C: inhibiting rate summation；D: maximal percentage inhibition；
E: minimum inhibiting rate.
The results are shown in Table 1, and the anticancer activity of compound 1,2 and 3 is very strong.
The 503nhibiting concentration of 11,2 and 3 couple of Hela of compound of table
2) using the inhibiting effect of mtt assay research 1,2 and 3 couple of HepG2 of compound.
Concrete operations: the HepG2 cell to be tested of logarithmic growth phase is configured to 105The single cell suspension of a/milliliter,
Be inoculated on 96 well culture plates, 100 microlitres of every hole, in volume fraction be 5% carbon dioxide, saturated humidity, 37 DEG C of incubators
Middle culture one day；Later, the sample to be tested of 100 microlitres of various concentrations is added on culture plate, every kind of concentration is 2 multiple
Hole；After continuing culture for 24 hours, every hole adds 20 microlitres of MTT dyeing liquor, continues to cultivate 4h in the incubator, careful removal upper layer is clear
Liquid, then every hole adds 200 microlitres of THF, after half an hour fullys shake, measures OD sample value, experiment at 595nm wavelength in microplate reader
Blank group be to replace sample with the DMEM culture solution of 100 microlitres of serum-frees, absorbance value at this moment is OD blank value, is passed through
Formula (1) calculates sample to HepG2 cell inhibitory rate:
M=1-n=1-ODSample/ODBlank (1)
In formula, m: inhibiting rate；N: cell survival rate.
Then by formula (2), IC is calculated50:
lgIC50=a-b (c- (3-d-e)/4) (2)
In formula, a:lg maximum concentration；B:lg (maximum concentration/adjacent concentration)；C: inhibiting rate summation；D: maximal percentage inhibition；
E: minimum inhibiting rate.
The results are shown in Table 2, and the anticancer activity of compound 1,2 and 3 is very strong.
The 503nhibiting concentration of 21,2 and 3 couple of HepG2 of compound of table
| Compound | IC50/μmol/L |
| 1 | 11.69 |
| 2 | 10.87 |
| 3 | 15.87 |
3) using the inhibiting effect of mtt assay research 1,2 and 3 couple of Huvec of compound.
Concrete operations: the Huvec cell to be tested of logarithmic growth phase is configured to 105The single cell suspension of a/milliliter,
Be inoculated on 96 well culture plates, 100 microlitres of every hole, in volume fraction be 5% carbon dioxide, saturated humidity, 37 DEG C of incubators
Middle culture one day；Later, the sample to be tested of 100 microlitres of various concentrations is added on culture plate, every kind of concentration is 2 multiple
Hole；After continuing culture for 24 hours, every hole adds 20 microlitres of MTT dyeing liquor, continues to cultivate 4h in the incubator, careful removal upper layer is clear
Liquid, then every hole adds 200 microlitres of THF, after half an hour fullys shake, measures OD sample value, experiment at 595nm wavelength in microplate reader
Blank group be to replace sample with the DMEM culture solution of 100 microlitres of serum-frees, absorbance value at this moment is OD blank value, is passed through
Formula (1) calculates sample to HepG2 cell inhibitory rate:
M=1-n=1-ODSample/ODBlank (1)
In formula, m: inhibiting rate；N: cell survival rate.
Then by formula (2), IC is calculated50:
lgIC50=a-b (c- (3-d-e)/4) (2)
In formula, a:lg maximum concentration；B:lg (maximum concentration/adjacent concentration)；C: inhibiting rate summation；D: maximal percentage inhibition；
E: minimum inhibiting rate.
The results are shown in Table 3: 1,2 and 3 couple of Huvec of compound has weaker toxic side effect.
The 503nhibiting concentration of 31,2 and 3 couple of Huvec of compound of table
| Compound | IC50/μmol/L |
| 1 | 28.45 |
| 2 | 8.52 |
| 3 | 11.97 |
Claims (1)
1.N-6- methyl -3- pyridine acyl-dehydroabietylamine derivatives application in preparation of anti-tumor drugs；The tumour is
Hela,HepG2；N-6- methyl -3- pyridine acyl-the dehydroabietylamine derivatives obtain structural formula are as follows:
In formula, R1For H, Cl, CH3。
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101580477A (en) * | 2009-06-18 | 2009-11-18 | 南京林业大学 | Dehydroabietylamine derivatives and application thereof in bactericidal and antineoplastic medicaments |
| WO2012078667A2 (en) * | 2010-12-06 | 2012-06-14 | The Penn State Research Foundation | Compositions and methods relating to proliferative diseases |
| CN102603561A (en) * | 2009-06-18 | 2012-07-25 | 南京林业大学 | Dehydroabietylamine derivatives and application thereof in preparation of antitumor drugs |
| CN102807495A (en) * | 2012-08-22 | 2012-12-05 | 中国林业科学研究院林产化学工业研究所 | 3-chlorine-2-hydroxypropyl dimethyl dehydroabietic-base ammonium chloride and preparation method thereof |
| CN103922961A (en) * | 2014-04-09 | 2014-07-16 | 南京林业大学 | Alkyl diol diphenyl ether dehydroabietylamine bis-Schiff base compound and synthetic method thereof |
-
2016
- 2016-07-26 CN CN201610597221.0A patent/CN106220559B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101580477A (en) * | 2009-06-18 | 2009-11-18 | 南京林业大学 | Dehydroabietylamine derivatives and application thereof in bactericidal and antineoplastic medicaments |
| CN102603561A (en) * | 2009-06-18 | 2012-07-25 | 南京林业大学 | Dehydroabietylamine derivatives and application thereof in preparation of antitumor drugs |
| WO2012078667A2 (en) * | 2010-12-06 | 2012-06-14 | The Penn State Research Foundation | Compositions and methods relating to proliferative diseases |
| CN102807495A (en) * | 2012-08-22 | 2012-12-05 | 中国林业科学研究院林产化学工业研究所 | 3-chlorine-2-hydroxypropyl dimethyl dehydroabietic-base ammonium chloride and preparation method thereof |
| CN103922961A (en) * | 2014-04-09 | 2014-07-16 | 南京林业大学 | Alkyl diol diphenyl ether dehydroabietylamine bis-Schiff base compound and synthetic method thereof |
Non-Patent Citations (7)
| Title |
|---|
| (+)-Dehydroabietylamine derivatives target triple-negative breast cancer;Taotao Ling等;《European Journal of Medicinal Chemistry》;20150723;第102卷;第9-13页 |
| Antitumor and scavenging radicals activities of some polyphenols related to dehydroabietylamine derivatives;Chao-Xiang Liu等;《Journal of Asian Natural Products Research》;20130625;第15卷(第8期);第819-827页 |
| ESSAY ON ANTIBIOTIC PROPERTIES OF ABIETYL COMPOUNDS;M. Mzlftic M. D;《Quarterly Journal of Crude Drug Research》;19701231;第10卷(第3期);第1606页表X化合物6 |
| N-Benzoyl-12-nitrodehydroabietylamine-7-one, a novel dehydroabietylamine derivative, induces apoptosis and inhibits proliferation in HepG2 cells;Ling-Ying Lin等;《Chemico-Biological Interactions》;20120625;第199卷(第2期);全文，尤其是第66页表1、第67页图2、第68页，补充数据表S2化合物63-66、图S1 |
| Synthesis and antitumour activities of a novel class of dehydroabietylamine derivatives;Yong Chen等;《Natural Product Research》;20120111;第26卷(第23期);第2188-2195页 |
| 实用高效的酰胺键形成试剂;王哲清;《中国医药工业杂志》;20061231;第37卷(第12期);第855-858页 |
| 脱氢枞胺衍生物DHAA-urea对人肝癌HepG2细胞糖代谢的抑制作用;谢建翔，等;《中国药科大学学报》;20101231;第41卷(第2期);第160-165页 |
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